Drug addiction

Drug addiction, or substance dependence is the compulsive use of drugs, to the point where the user has no effective choice but to continue use. This phenomenon has occurred to some degree throughout recorded history (see "opium"), though modern agricultural practices, improvements in access to drugs, and advancements in biochemistry have exacerbated the problem significantly in the 20th century with the introduction of purified forms of active biological agents, and with the synthesis of hitherto unknown substances, such as methamphetamine and gamma-hydroxybutyrate (GHB). While "addiction" has been replaced by "dependency" as a clinical term, the terms are used interchangeably here.

The chemicals responsible

The CREB protein, a transcription factor activated by cyclic adenosine monophosphate (cAMP) immediately after a high, triggers genes that produce proteins such as dynorphin, which cuts off dopamine release and temporarily inhibits the reward circuit. In chronic drug users, a sustained activation of CREB leaves the user feeling depressed and dissatisfied, and unable to find pleasure in previously enjoyable activities, often leading to a return to the drug for an additional "fix". It also leads to a short term tolerance of the substance, necessitating that a greater amount be taken in order to reach the same high.

Related Topics:
CREB - Transcription factor - Cyclic adenosine monophosphate - Gene - Dynorphin

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Another transcription factor, known as delta FosB, is thought to activate genes that, counter to the effects of CREB, actually increase the user's sensitivity to the effects of the substance. Delta FosB slowly builds up with each exposure to the drug and remains activated for weeks after the last exposure?long after the effects of CREB have faded. The hypersensitivity that it causes is thought to be responsible for the intense cravings associated with drug addiction, and is often extended to even the peripheral cues of drug use, such as related behaviors or the sight of drug paraphernalia. There is some evidence that delta FosB even causes structural changes within the nuclear accumbens, which presumably helps to perpetuate the cravings, and may be responsible for the high incidence of relapse that occur in treated drug addicts.

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